This invention relates generally to polymer-supported catalysts having pyridylamino functionality, and in particular to a cross-linked copolymer of vinyl-substituted 4-(N-benzyl-N-methylamino)pyridine and a styrene monomer derivative characterized by improved physical properties and marked catalytic activity, and further to an improved acid salt form of the 4-(N-benzyl-N-methylamino)pyridine monomer and the use of the same for preparing polymer-supported catalysts.
By way of general background, it has been recognized for some time that 4-dimethylaminopyridine (commonly referred to as "DMAP") and certain of its dialkylamino analogs are highly effective catalysts for acylations, alkylations and other related reactions. Hofle, G., Steglich, W., Vorbruggen, H., Angew. Chem. Int. Ed. Engl., 17, 569 (1978); Scriven, E. F. V., Chem. Soc. Rev., 129 (1983). Also recognized for some time has been the desirability of a polymer-bound or supported version of such DMAP-like catalysts in view of the potential advantages of ease of recovery and repeated use along with the adaptability of such catalysts in both static and flow systems. Although such polymers could be soluble, it is understood that insoluble, heterogeneous gel or macroreticular resin beads provide the greater advantages in ease of removal and recyclability. Frechet, J. M. J., Deratani, A., Darling, G, Lecavalier, P., Li, N. H., Macromol. Chem. Macromol. Symp., 1 91 (1986); Patchornik, A., Chemtech, January, 1987, 58.
Accordingly, much investigation has taken place in search of an effective polymer-supported DMAP-like catalyst. For example, Klotz and his coworkers were the first to report such a polymer made by attaching an acid-functionalized dialkylaminopyridine to a polyethyleneimine polymer. Hierl, M. A., Gamson, E. P., Klotz, I. M., J. Am. Chem. Soc.. 101. 6020 (1979). Klotz in combination with others subsequently reported similar functionalized polyimines, and demonstrated their catalytic ability by kinetic experiments on the hydrolysis of .rho.-nitrophenyl caproate. Delaney, E. J., Wood, L. E., Klotz., I. M., J. Am. Chem. Soc., 104. 799 (1982); Klotz, I. M., Massil, S. E., Wood, L. E., J. Polymer Sc., Polymer Chem. Ed., 23, 575 (1985). These polymers suffered, however, from the drawback that the pyridine was attached to the polymer backbone by an amide linkage which was susceptible to scission as when regenerating the resin using sodium hydroxide in acetylation reactions involving acyl halides.
Verducci and his coworkers reported attaching 4-piperidinylpyridine, among other DMAP-like moieties, to a Merrifield resin also through an amide bond. Guendouz, F., Jacquier, R., Verducci, J., Tetrahedon Lett., 25, 4521 (1984). The amide bond in this polymer, however, was reported to stand up well on recycle in the catalytic acetylation of 1-methylcyclohexanol at 70.degree. C. and 24 hours.
Nevertheless, more popular approaches to achieve DMAP-like polymer catalysts have avoided the use of amide linkages altogether. For example, Shinkai and his coworkers reported attaching 4-chloropyridine to an aminomethylpolystyrene to yield a polymer-supported 4-(N-benzyl-N-methylaminq)pyridine (which functional group has commonly become known as "BMAP"). Shinkai, S., Tsuji, H., Hara, Y., Manabe, O., Bull. Chem. Soc. Jpn., 54, 631 (1981). This polymer-bound BMAP material was reported to effectively catalyze simple esterifications, but the product achieved by Shinkai had the disadvantages of including a high percentage of a secondary amine which interfered with the reaction unless alkylated prior to use.
Another group of investigators led by Tomoi has compared two other approaches to achieve a similar polymeric BMAP catalyst. Tomoi, M., Akada, Y., Kakiuchi, H., Macromol. Chem., Rapid Commun., 3, 537 (1982). Tomoi reported, among other things, that a route involving copolymerization of the preformed BMAP monomer gave a better catalyst product. However, more recently a group led by Frechet challenged this conclusion, reporting that preformed chloromethylated polystyrene can be modified readily and quantitatively to produce an even better catalyst. Frechet, J. M. J., Deratani, A., Darling, G, Lecavalier, P., Li, N. H., Macromol. Chem. Macromol. Symp., 1, 91 (1986). Menger and his coworkers have also reported success in converting a linear chloromethylpolystyrene resin to the corresponding linear BMAP polymer which has proven effective in well-known DMAP-catalyzed processes such as the conversion of linalool to linalyl acetate which has definite commercial interest. Menger, F. M., McCann, D. J., J. Org. Chem. 50, 3928 (1985).
The extent of work in this field has also led groups headed by Frechet, Tomoi, Manecke and Challa to study the effects of variation of the frequency of BMAP-to-styrene units as well as variations of cross-linking and of the length and nature of the spacer arm or component separating the pyridylamino functional group from the polymer backbone. To this end, numerous polymers have been reported by these groups with varying degrees of detail. Deratani, A., Darling, G. D., Horak, D., Frechet, J. M. J., Macromolecules, 20, 767 (1987); Deratani, A., Darling, G. D., Frechet, J. M. J., Polymer 28, 825-830 (1987); 10th Intl. Conf. Heterocycl. Chem. (1985); Tomoi, M., Goto, M., Kakiuchi, H. J., Polym. Sc., Polym. Chem., 25, 77 (1987); Storck, W., Manecke, G., J. Mol. Cat., 30, 145 (1985); and Koning, C. E., Eshuis, J. J. W., Viersen, F. J., Challa, G., Reactive Polym., 4, 293 (1986).
In reviewing these collective efforts, as highlighted above, it is evident that the paramount interest to date has been to confirm the ability to synthesize polymer-supported catalysts of these types approaching DMAP activity. Accordingly, little or no effort has gone into characterizing in a quantitative or qualitative way the physical or chemical properties of the polymer compounds thus far obtained. Nevertheless, these same properties dictate the ultimate commercial utility of such polymeric catalysts in whatever reactions they are used.
For example, while these considerable scientific publications have demonstrated the general or potential utility of polymeric catalysts of this type, nearly all have done so with polymers having low degrees of cross-linking up to only about 2% by weight of the total polymerizable monomer present. These prior art polymers have been reported and proven to be mechanically weak and to exhibit noticeable breakage and disintegration both as formed and during use, particularly with even moderate attempts at recycling. In addition, these polymers have exhibited substantial swelling in excess of 100-200% by volume upon exposure to a solvent which has aggravated breakage upon recapture. This is a definite disadvantage in many commercial processes, for example, where space constraints are important.
Moreover, these polymers prepared according to the literature references contain significant amounts of granular powders, flake or other irregular shapes instead of the predominant bead form that is preferred. Such unwanted particles are mechanically unstable and suitable for use only in stirred-slurry or other reactors where clogging of filters or lines is not a concern and where recycling of the catalyst is not contemplated. The gel-type bead segments that are present in these reference materials are nonuniform in size or configuration, exhibit great deviation from the average or median size present, and do not show the durable, hard form that is preferred. While Frechet has reported making a 34% divinylbenzene (DVB) cross-linked macroreticular resin also within this class, he reported and subsequent testing has confirmed that it has inferior chemical and physical properties as a catalyst in the acylation of 1-methylcyclohexanol. In addition, Frechet's resin made from his preferred chloromethylated polystyrene process may contain quaternary salt from unwanted side reactions which can react to ring-open under strongly basic conditions as often encountered.
Therefore, while certain publications have reported the synthesis of polymer-supported DMAP-like resins and their general catalytic ability, there has been and remains today the need for a catalyst of this type in both gel and macroreticular form that exhibits overall mechanical stability as expected with higher degrees of cross-linking while retaining effective chemical properties believed lost in such materials. Improved physical properties of surface texture and configuration, uniformity and durability are also desired, as are chemical properties approaching the catalytic potency and universal acceptance of DMAP and its analogs.
Further, difficulties in handling the BMAP monomer starting material have been encountered. In particular, BMAP monomer in its free base form is quite reactive. As a monomer related to styrene, BMAP monomer tends to polymerize readily and does not survive manipulations well. For example, even distillation in a falling film still under high vacuum produces very low recovery of BMAP monomer free base. Purification by crystallization is also difficult as BMAP monomer free base is a low melting solid. Consequently, present preparations of polymer-supported 4-(N-benzyl-N-methylamino)pyridine catalysts employ relatively impure BMAP monomer.
In synthesizing the free base, the BMAP monomer according to the references above is generally isolated as a solution of a crude product which may contain a number of useless, even interfering, by-products. Among these may be mineral oil, unreacted vinylbenzyl chloride and 4-methylaminopyridine (MAP). Additional unknown compounds and intractable materials are also present. The presence of these by-products in the BMAP monomer starting material, and the previous inability to effectively purify it, have detracted from the purity of the catalyst product and resultantly from its efficient and effective use.
Also, the polymerizations themselves have been required to be carried out relatively quickly after synthesis of the BMAP monomer due to its reactivity and inherent instability. As a result, preparation of the monomer has been limited to the quantity needed for immediate use as the free base cannot be stored for any appreciable length of time pending further use. Preparation of quantities of monomer exceeding amounts immediately consumable have typically resulted in loss of this excess and waste of the materials.